A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion

Sandra M. Newton, Rebecca J. Smith, Katalin A. Wilkinson, Mark P. Nicol, Natalie J. Garton, Karl J. Staples, Graham R. Stewart, John R. Wain, Adrian R. Martineau, Sarah Fandrich, Timothy Smallie, Brian Foxwell, Ahmed Al-Obaidi, Jamila Shafi, Kumar Rajakumar, Beate Kampmann, Peter W. Andrew, Loems Ziegler-Heitbrock, Michael R. Barer, Robert J. Wilkinson

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519, but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage.

Original languageEnglish
Pages (from-to)15594-15598
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number42
DOIs
Publication statusPublished - 17 Oct 2006
Externally publishedYes

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